Symptoms of disease

The symptoms of familial chylomicronemia syndrome result directly from the elevated levels of chylomicrons and triglycerides in the bloodstream.  Pancreatitis, inflammation of the pancreas, is the most serious symptom, and it is often the first presenting symptom for individuals with this condition.  Pancreatic lipase produced by the pancreas partially breaks down the excess chylomicrons, causing irritation and inflammation of the pancreas.   The abdominal pain, which can be quite severe, often radiates to the back.  Nausea and vomiting occur as well.  Patients often need to be hospitalized for treatment; in some cases the pancreatitis leads to life threatening complications.  It has been estimated that about 7% of cases of pancreatic may be due to this condition, sometimes undiagnosed.

The pancreatitis may be recurrent, especially if the condition is not yet diagnosed or not being adequately treated, resulting in the need for multiple hospital stays.  Over time this can damage the pancreas, diminishing its ability to secrete its normal enzymes and hormones.  This can result in the secondary conditions of diabetes, fatty stools, pancreatic calcification, and also in an increased risk of pancreatic cancer.

Eruptive xanthomas also may occur.  These are fatty deposits in the skin, most commonly on the soles of the feet, knees, elbows, or on the back or buttocks, though they can form anywhere on the skin.  They usually develop over areas of injury or pressure.  Sometimes these are very small, but other times they may be bigger than three inches in diameter.  Generally they do not hurt, and they tend to disappear a few weeks to months after the chylomicrons and triglyceride levels are returned to normal.  Imaging may reveal fatty deposits on other tissues, such as the spleen and kidneys.  Imaging may also show an enlarged liver and spleen (hepatosplenomegaly) which results when these organs take up the excess chylomicrons.  Blood vessels in the eye may also turn white due to fat deposits (lipemia retinalis), but this does not affect vision.

Recurrent abdominal pain, nausea, and diarrhea may also occur independent of outright pancreatitis.  Other symptoms may include headaches and pain in the muscles or bones.  More rarely neurological symptoms may occur, like memory difficulties, tingling or burning sensation in the hands or feet (neuropathy), and depression.  Increased risk of gallstones has been noted.

Traditionally it was thought that the condition did not carry an increased risk of atherosclerosis, unlike many other dyslipidemias.  However, some recent evidence shows that individuals with familial chylomicronemia may have a slightly increased risk of atherosclerosis, leading to increased risk of heart attack and stroke.  These patients may also be at increased risk of chest pain.

Infants with chylomicronemia may not gain weight normally—a condition known as “failure to thrive.”  These infants may be jaundiced and colicky with increased irritability, and they may also suffer pancreatitis.

Sometimes an individual may have no symptoms on diagnosis.  These individuals may be identified due to abnormal lab values before clinical symptoms have developed or sometimes after a genetic screen.

The symptoms and disease course vary significantly between individuals.  Some mutations are more severe, leading to increased levels of chylomicrons and triglycerides, and manifesting with increased symptoms appearing earlier in life.   Patients with the Apo CII mutation do not usually display xanthomas or hepatosplenomegaly.  Recent diet plays a large role in frequency and severity of symptoms.  Patients find their symptoms worsen after eating meals too high in fat; many symptoms resolve if the recommended diet is strictly followed.